Therapeutic innovation & regulatory science最新文献

{"title":"Consumer Understanding of Prescription Drug Indications in Direct-to-Consumer Television Advertisements.","authors":"Helen W Sullivan, Kathryn J Aikin, Mihaela Johnson, Kate Ferriola-Bruckenstein","doi":"10.1007/s43441-024-00732-4","DOIUrl":"10.1007/s43441-024-00732-4","url":null,"abstract":"<p><strong>Background: </strong>Prescription drugs may be indicated to treat more than one medical condition, and companies may promote more than one indication in the same direct-to-consumer (DTC) ad. This study examined how presenting multiple prescription drug indications in one DTC television ad affects consumers' processing of drug information.</p><p><strong>Methods: </strong>We conducted two studies with adults diagnosed with diabetes (Study 1, N = 408) or rheumatoid arthritis (Study 2, N = 411). We randomly assigned participants to view one of three television ads: primary indication only (Study 1: diabetic peripheral neuropathy; Study 2: rheumatoid arthritis), primary plus a similar secondary indication (Study 1: fibromyalgia; Study 2: psoriatic arthritis), or primary plus a dissimilar secondary indication (Study 1: generalized anxiety disorder; Study 2: ulcerative colitis).</p><p><strong>Results: </strong>Remembering and understanding the primary indication was not significantly affected by the presence of a secondary indication (similar or dissimilar). Higher health literacy participants remembered and understood secondary indications.</p><p><strong>Conclusions: </strong>Including a second indication in DTC television ads does not appear to have detrimental effects and can increase awareness of the second indication for some participants. Industry and regulators should continue to ensure DTC promotion is truthful and non-misleading, irrespective of the number of indications presented.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inside the Mind of the DMC: A Review of Principles and Issues with Case Studies.","authors":"Lizhao Ge, Toshimitsu Hamasaki, Scott R Evans","doi":"10.1007/s43441-024-00720-8","DOIUrl":"https://doi.org/10.1007/s43441-024-00720-8","url":null,"abstract":"<p><p>A data monitoring committee (DMC) can have an extremely challenging job. Stop a trial too soon, and results are inconclusive and the trial fails to obtain answers to important questions that could inform future clinical practice. Stop a trial too late, and trial participants are exposed to potentially harmful or ineffective interventions longer than necessary. Securing convincing and conclusive evidence and the ethical responsibility to current and future patients are weighed carefully during DMC deliberations. The ability to interpret complex information, and appreciation of issues affecting scientific integrity, are critical for the DMC to protect trial participants and public trust. Challenges faced by and issues of prudence faced by DMCs are discussed including interim analysis issues, assessing the totality of information with statistical boundaries as guidelines, interpretation of composite and surrogate outcomes, reactions to early trends, benefit:risk assessment, landscape changes, subgroup analyses, composing information for a comprehensive understanding of patient-centric effects, and evaluating the value of additional data. Case studies illustrate how DMCs addressed the challenges.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mixture Disease Progression Model to Predict and Cluster the Long-Term Trajectory of Cognitive Decline in Alzheimer's Disease.","authors":"Ryoichi Hanazawa, Hiroyuki Sato, Akihiro Hirakawa","doi":"10.1007/s43441-024-00708-4","DOIUrl":"https://doi.org/10.1007/s43441-024-00708-4","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disease for which many clinical trials failed to detect treatment effects, possibly due to the heterogeneity of disease progression among the patients. Predicting and clustering a long-term trajectory of cognitive decline from the short-term cognition data of individual patients would help develop therapeutic interventions for AD.</p><p><strong>Methods: </strong>This study developed mixture disease progression model to predict and cluster the long-term trajectory of cognitive decline in the population. We predicted the 30-year long-term trajectories of the three cognitive scales and categorized the individuals into rapid and slow cognitive decliners by applying the method, which was based on the two-component normal mixture nonlinear mixed-effects model, to the short-term follow-up data of the Mini-Mental State Examination, the 13-item Alzheimer's Disease Assessment Scale-Cognitive, and the Clinical Dementia Rating Scale-sum of boxes collected in patients with mild cognitive impairment and AD in the Alzheimer's Disease Neuroimaging Initiative.</p><p><strong>Results: </strong>For each cognitive scale, the models identified two distinct subpopulations, including a population of comprising approximately 10-20% of individuals experiencing rapid cognitive decline, wherein the posterior means of the differences in cognitive decline speed between the two groups ranged from 2 to 3 years. We also identified baseline background factors associated with rapid decliners for three cognitive scales.</p><p><strong>Conclusion: </strong>Identifying the risk factors associated with rapid decline of cognition by the proposed method aids in planning eligibility criteria and allocation strategy for accounting for the varying disease progression speeds among the patients enrolled in clinical trials for AD.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk-Based Quality Management: A Case for Centralized Monitoring.","authors":"Nicole Stansbury, Danilo Branco, Cris McDavid, Jennifer Stewart, Kristin Surdam, Nycole Olson, Joanne Perry, Jeremy Liska, Linda Phillips, Amanda Coogan, Anina Adelfio, Lauren Garson","doi":"10.1007/s43441-024-00719-1","DOIUrl":"https://doi.org/10.1007/s43441-024-00719-1","url":null,"abstract":"<p><p>Since 2019, the Association of Clinical Research Organizations has conducted a landscape survey of risk based quality management (RBQM) adoption in clinical trials. Here, we present data from four years of surveys, with an emphasis on the most recent: the 2022 survey included data from 4958 trials across seven contract research organizations, of which 1004 were new studies started in 2022. Results indicate that while overall risk assessment adoption is strong, it is lagging in other risk-based components which suggests companies are not deriving the full expected benefits of performing a risk assessment and mitigation process to their trials. The 2022 study also suggests new study starts showing promising traction, with adoption hovering near 50% for most RBQM elements. At the same time, the survey suggests industry has mixed views on the potential value of quality tolerance limits (QTLs). Ultimately, centralized monitoring is being underutilized despite the potential of increased patient safety oversight and improved data quality. The authors of this paper developed a case study based on a trial in clinicaltrials.gov to demonstrate how RBQM adoption could include the key RBQM elements such as centralized monitoring, reduced source data review and source data verification as well as implementation of QTLs in a real-world scenario. The authors believe the clinical trial industry has an obligation to utilize centralized monitoring to produce more efficient and effective clinical trials and will make a case to do so in this paper.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data Monitoring Committee Reports: Telling the Data's Story.","authors":"Lijuan Zeng, Toshimitsu Hamasaki, Scott R Evans","doi":"10.1007/s43441-024-00727-1","DOIUrl":"https://doi.org/10.1007/s43441-024-00727-1","url":null,"abstract":"<p><p>A Data Monitoring Committee (DMC) plays a pivotal role in monitoring participant safety and efficacy and overseeing the integrity of clinical trials. DMCs accomplish this mission by periodically reviewing accumulating data to assess benefits and harms of interventions in ongoing studies and making subsequent recommendations regarding future clinical trial conduct to the trial sponsor. Reports summarizing data from the clinical trial are prepared for the DMC by statistical and data analysis centers to inform DMC decision-making. In practice however, these reports are often disorganized, complex, and provide overwhelming detail yet insufficient information, that hinders accurate and efficient interpretation of interim data. This review paper delves into the nuances of preparing effective DMC reports, highlighting the importance of simplicity, clarity, and thoughtful relevance in data presentation. We discuss structured approaches for preparing closed reports, which deal with sensitive and sometimes messy interim data, and underscore the use of visual summaries and narrative elements that enhance comprehension and facilitate efficient assessments of trial data. The paper outlines key principles for preparing DMC reports and provides practical guidance on their structure. Ultimately, this guidance seeks to ensure that the data's story is clearly and efficiently conveyed to facilitate the DMC decision-making process.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Call for Papers: The Inflation Reduction Act and Its Impact on Innovation, Access, and Affordability.","authors":"Gregory Daniel","doi":"10.1007/s43441-024-00721-7","DOIUrl":"https://doi.org/10.1007/s43441-024-00721-7","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging Real-World Data in Safety Signal Assessment.","authors":"Vaishali Patadia, Katrin Manlik, Geoffrey Gipson, Jenna C Willis, Ruth Namuyinga, Rachel McDermott, Anita Shaw, Mary K Miller, Julius Asubonteng, Negar Golchin, Stephanie von Klot","doi":"10.1007/s43441-024-00682-x","DOIUrl":"10.1007/s43441-024-00682-x","url":null,"abstract":"<p><strong>Purpose: </strong>TransCelerate BioPharma surveyed its member biopharmaceutical companies to understand current practices and identify opportunities to complement safety signal assessment with rapid real-world data (RWD) analysis.</p><p><strong>Methods: </strong>A voluntary 30-question questionnaire regarding the use of RWD in safety signal assessment was disseminated to subject matter experts at all TransCelerate member companies in July 2022. Responses were blinded, aggregated, summarized, and presented.</p><p><strong>Results: </strong>Eighteen of 20 member companies provided responses to the questionnaire. Sixteen (89%) companies reported actively leveraging RWD in their signal assessment processes. Of 18 respondent companies, 8 (44%) routinely use rapid approaches to RWD analysis, 7 (39%) utilize rapid RWD analysis non-routinely or in a pilot setting, 2 (11%) are considering using rapid RWD analysis, and 1 (6%) has no plans to use rapid RWD analysis for their signal assessment. Most companies reported that RWD adds context to and improves quality of signal assessments. To conduct RWD analysis for signal assessment, 16 of 17 (94%) respondent companies utilize or plan to utilize internally available data, 8 (47%) utilize both internal and external data, and 3 (18%) utilize data networks. Respondents identified key challenges to rapidly performing RWD analyses, including data access/availability, time for analysis execution, and uncertainties regarding acceptance of minimal or non-protocolized approaches by health authorities.</p><p><strong>Conclusion: </strong>Biopharmaceutical companies reported that they see value in the use of rapid RWD analyses for complementing signal assessments. Future work is recommended to offer a framework and process for use of rapid use of RWD analyses in signal assessment.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1062-1070"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using a Quality Management System and Risk-based Approach in Observational Studies to Obtain Robust Real-World Evidence.","authors":"Reo Tanoshima, Naoko Inagaki, Manabu Nitta, Soichiro Sue, Sayuri Shimizu, Tatsuya Haze, Kotaro Senuki, Chihiro Sano, Hajime Takase, Makoto Kaneko, Akito Nozaki, Kozo Okada, Kohei Ohyama, Atsushi Kawaguchi, Yusuke Kobayashi, Hideki Oi, Shin Maeda, Yuichiro Yano, Yuji Kumagai, Etsuko Miyagi","doi":"10.1007/s43441-024-00695-6","DOIUrl":"10.1007/s43441-024-00695-6","url":null,"abstract":"<p><p>The results of observational studies using real-world data, known as real-world evidence, have gradually started to be used in drug development and decision-making by policymakers. A good quality management system-a comprehensive system of process, data, and documentation to ensure quality-is important in obtaining real-world evidence. A risk-based approach is a common quality management system used in interventional studies. We used a quality management system and risk-based approach in an observational study on a designated intractable disease. Our multidisciplinary team assessed the risks of the real-world data study comprehensively and systematically. When using real-world data and evidence to support regulatory decisions, both the quality of the database and the validity of the outcome are important. We followed the seven steps of the risk-based approach for both database selection and research planning. We scored the risk of two candidate databases and chose the Japanese National Database of designated intractable diseases for this study. We also conducted a quantitative assessment of risks associated with research planning. After prioritizing the risks, we revised the research plan and outcomes to reflect the risk-based approach. We concluded that implementing a risk-based approach is feasible for an observational study using real-world data. Evaluating both database selection and research planning is important. A risk-based approach can be essential to obtain robust real-world evidence.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1006-1013"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the State of Pharmacovigilance in Secondary Hospitals in the Federal Capital Territory of Nigeria, Using WHO Pharmacovigilance Indicators.","authors":"Augustus Chukwuebuka Ezeodimegwu, Francis Chibuike Iloabuchi, Ifunanya Mary-Ann Onyia, Cynthia Chidubem Eze, Gabriel Ezenri, Princess Chidimma Onyekwuo, Chukwuebuka Vincent Ihemegbulam, Abdulmuminu Isah","doi":"10.1007/s43441-024-00703-9","DOIUrl":"10.1007/s43441-024-00703-9","url":null,"abstract":"<p><strong>Background: </strong>The importance of pharmacovigilance (PV) in ensuring drug safety, especially in the detection and prevention of adverse drug reactions (ADRs) is critical. However, PV activities in Nigeria still face many challenges, such as very low spontaneous reporting rates, and inadequate training and funding. This study assessed the state of pharmacovigilance in the federal capital territory of Nigeria (FCT), using WHO pharmacovigilance indicators.</p><p><strong>Methods: </strong>A cross-sectional questionnaire-based survey was carried out among secondary healthcare facilities in the FCT. The WHO Pharmacovigilance Indicators Questionnaire, which consists of the structural, process and outcome measures, was used to collect data from the focal person for pharmacovigilance at all the consenting facilities. Descriptive statistics were used to summarize all variables. Ethical approval was obtained from the Ethics Review Committee of the FCT development authority.</p><p><strong>Results: </strong>Of the 14 secondary healthcare facilities in the FCT, 11 agreed to the study (response rate = 84.6%). Among the respondents, 4 (36.4%) were females, and 2 (18.2%) had 9 years of experience in pharmacovigilance. For the core structural indicators, 7 (63.6%) of the facilities had a pharmacovigilance center while only 4 (36.4%) had a copy of the Nigerian pharmacovigilance policy. Regarding financial provisions, 10 (90.9%) hospitals reported that there was no regular financial provision for the center while 10 (90.9%) centers had a standard adverse drug reaction reporting form. For the core process indicators, the mean ± SD of the nine core process indicators ranged from 0.9 ± 3.0 to 75.6 ± 38.6 and the total number of reports in the local database, therapeutic ineffectiveness, and medication error were limited.</p><p><strong>Conclusion: </strong>The assessment of pharmacovigilance activities in the Federal Capital Territory of Nigeria revealed significant gaps in infrastructure, financial support, and process implementation. Despite the presence of pharmacovigilance centers in the majority of facilities, the lack of consistent financial support and limited adherence to core process indicators highlight the need for enhanced training, resources, and policy enforcement to improve ADR reporting and overall drug safety monitoring. Strengthening these areas is crucial for advancing pharmacovigilance practices and ensuring patient safety in Nigeria.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1148-1158"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tips for Accelerating BOIN Design.","authors":"Masahiro Kojima, Wu Wende, Henry Zhao","doi":"10.1007/s43441-024-00692-9","DOIUrl":"10.1007/s43441-024-00692-9","url":null,"abstract":"<p><p>During discussions at the Data Science Roundtable meeting in Japan, there were instances where the adoption of the BOIN design was declined, attributed to the extension of study duration and increased sample size in comparison to the 3 + 3 design. We introduce an accelerated BOIN design aimed at completing a clinical phase I trial at a pace comparable to the 3 + 3 design. Additionally, we introduce how we could have applied the BOIN design within our company, which predominantly utilized the 3 + 3 design for most of its clinical oncology dose escalation trials. The accelerated BOIN design is adaptable by using efficiently designated stopping criterion for the existing BOIN framework. Our approach is to terminate the dose escalation study if the number of evaluable patients treated at the current dose reaches 6 and the decision is to stay at the current dose for the next cohort of patients. In addition, for lower dosage levels, considering a cohort size smaller than 3 may be feasible when there are no safety concerns from non-clinical studies. We demonstrate the accelerated BOIN design using a case study and subsequently evaluate the performance of our proposed design through a simulation study. In the simulation study, the average difference in the percentage of correct MTD selection between the accelerated BOIN design and the standard BOIN design was - 2.43%, the average study duration and the average sample size of the accelerated BOIN design was reduced by 14.8 months and 9.22, respectively, compared with the standard BOIN design.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"1129-1137"},"PeriodicalIF":2.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}